Emery-Dreifuss Muscular Dystrophies

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder clinically characterized by the triad of slowly progressive muscle wasting and weakness in a humeroperoneal distribution in the early stages; early joint contractures of the elbows, Achilles tendons and spinal rigidity; and cardiac involvement with conduction defects, arrhythmias and cardiomyopathy. Thus far, six causative genes for EDMD have been identified including EMD (EDMD1), LMNA (EDMD2 and 3), SYNE1 (EDMD4), SYNE2 (EDMD5), FHL1 (EDMD6), and TMEM43 (EDMD7). All gene products are associated with the nuclear envelope. EDMD may be easy to diagnose when the characteristic clinical triad is present. However, some patients may not exhibit all three canonical features, especially in the early stages of the disease. Further, the marked intrafamilial and interfamilial phenotypic heterogeneity and the genetic diversity make its diagnosis difficult. Cardiac involvement is a common and probably the most important clinical feature of EDMD since it is directly related to the prognosis; life-threatening cardiac events can occur before the diagnosis of the muscular dystrophy. Histopathologic evidence of loss of emerin immunoreactivity in EDMD1 or presence of reducing bodies in some patients with EDMD6 serve as diagnostic clues, but genetic tests remain pivotal for the diagnosis. No disease specific treatment is available currently, but some potential therapeutic targets are proposed from basic research.